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6 August, 2019 10:52:45 AM

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Dengue: How much is too much?

Routine reporting of vector born diseases in national disease surveillance systems is the backbone of epidemiological information
Mohammed Abul Kalam, PhD
Dengue: How much is too much?

Winegard’s book offers a catalog of such stories. It turns out that, if you’re looking for them, the words “mosquitoes,” “fever,” “ague,” and “death” is repeated to the point of nausea throughout human history.

(And before Winegard suggests that when the asteroid hit, dinosaurs were already in decline from mosquito-borne diseases.)
As dengue (DENV) continues to spread countrywide, there is an ever-increasing need to develop and apply cost-effective, evidence-based approaches to identify and respond to arboviral disease outbreaks. Outbreak response should be timely (i.e., early enough to prevent the epidemic spread of the virus), coordinated among multiple stakeholders, and should make use of existing vector control interventions against Aedes populations the principal vector responsible for the transmission of these viruses.
Routine reporting of notifiable diseases in national disease surveillance systems is the backbone of epidemiological information; it is used to monitor the spatial and temporal distribution of different clinical expressions of diseases, to determine the risk and priority areas for interventions, and to trigger outbreak alerts. Dengue-endemic country surveillance and response systems were systematically reviewed to identify what corrective actions should be undertaken and how countries should be supported. Dengue surveillance was found to suffer from significant delays and marked underreporting, especially for non-hospitalized dengue cases. The comparative analysis of national dengue contingency plans revealed weak overall outbreak governance due to poor clarity of stakeholder roles, weak surveillance systems, inadequate use of routinely generated data and additional alerts in tandem, absence of outbreak definition, and absence of structured early response mechanisms.

Systematic reviews and country studies highlighted the critical characteristics of an efficient alert system to trigger responses: it should be sensitive to predict or detect outbreaks in a timely manner; specific to avoid unnecessary false alerts; and time to trigger an early response. In order for systems to meet these requirements, they should make use of a simplified and standardized case classification, be supported by laboratories using standardized and quality-controlled assays, include active/enhanced/syndromic surveillance, and either incorporate additional alarm signals or increase data quality and/or timeliness.

Laboratory diagnosis of dengue is currently done either by detecting the virus or its components (viral RNA by PCR or antigens likes NS1) or by detecting immune response by serological tests.

A confirmed case requires virus isolation, RNA detection, antigen detection, seroconversion for IgM, or a 4-fold rise in IgG titers; IgM positivity is considered highly suggestive. The timing of testing is critical, considering that both viraemia and NS1 are confined to the first week of illness, and IgM production is transient (lasting 5-6 months), while IgGlasts longer. Confirming dengue diagnosis is a clear challenge for countries, both at point of care and at referral facilities. ELISA appears to accurately identify >90% of primary and secondary dengue cases from a single serum specimen collected during the first 10 days of illness. While operationally and financially demanding, laboratory confirmation is important, both for clinical management and outbreak identification: it increases the specificity of the information captured by the surveillance system, contributes to syndromic surveillance (e.g., increased numbers of laboratory requests), and may generate serotype- or genotype-specific data as a potential additional outbreak alarm signal.

Syndromic surveillance (developed as an additional, often context-specific tool for early outbreak alert) is not limited only to clinical syndromes but may include increased numbers of school absenteeism, increased laboratory requests as described above or an increased proportion of positive laboratory results in the inter-epidemic period. These alarm signals can be then integrated into a risk assessment tool. Indeed, enhanced surveillance should aim to combine tools that complement routine reporting, not to replace it.

A range of variables that either indicate risk of forthcoming dengue transmission or predict dengue outbreaks have been suggested throughout the literature. The combination of these variables, or alarm indicators, for use in early warning systems, is the next natural step. An Early Warning and Response System (EWARS) has since been developed following a period of retrospective country dataset analysis, modeling, and prospective field evaluation.

These tools and materials will help build capacity in dengue-endemic settings. In addition, a technical handbook (model contingency plan) has been developed. It is intended to serve as a framework, incorporating all under the aspects of evidence described in ‘Outbreak preparedness of dengue epidemics’ above in order to support and guide the national contingency-planning process.

Following up the above-mentioned evidence, two additional areas of future development have emerged: (1) the ability to combine qualitative and quantitative variables into a broad-ranging early warning system, and (2) spatial risk-mapping tools that help to identify smaller spatial areas for fine-scale interventions.

I made a systematic review and meta-analysis evaluated the evidence of the effectiveness of vector control interventions in (a) reducing vector indices and (b) preventing dengue transmission. The searches covered all major indexing databases throughout the period 1980 - January 2013. The primary outcome was dengue incidence with secondary outcomes comprising a number of Aedes indices (e.g., Breteau Index, House Index, Container Index, mosquito adults per person, pupae per person); analyses were stratified by study design, intervention, and measures of effect and outcome. The main findings of the meta-analysis were: (1) moderate evidence that house screening can reduce vector abundance and emerging evidence that it reduces dengue transmission; (2) strong evidence that community-based campaigns can impact vector abundance, with emerging evidence for impact on transmission; and (3) no robust studies on the impact of fogging on transmission, with only one study showing an impact on Aedes albopticus.

A systematic literature review examined the published evidence investigating associations between vector indices and dengue cases. After assessment of the epidemiological study designs, all but three of the 18 studies were classified as methodologically weak. Heterogeneity among spatial/temporal sampling and analyses was high, perhaps demonstrating an absence of standardization for conducting such research. Of the 13 studies that investigated associations between vector indices and dengue cases, 4 reported positive correlations, 4 found no correlation, and 5 reported ambiguous or unreliable associations. Of the 7 studies that measured the Breteau Index, 6 reported dengue transmission at levels below the widely used threshold of 5.

Sampling vector populations, both for surveillance purposes and evaluation of control activities, is conducted annually worldwide. Further evidence of the relationship between vector indices and dengue transmission is necessary to better understand the impact of control activities on dengue incidence. Also, the role of asymptomatic individuals in virus transmission requires further analysis.

DENV transmission mainly occurs in urban and periurban areas usually consisting of large and heterogeneous districts. National programme managers, district health, and control programme staff urgently require a tool that identifies priority areas for action, particularly where the interventions should start, and ideally includes a rapid diagnostic test to distinguish between the different Aedes-borne diseases. In the presence of predictive outbreak alarms, a method to focus interventions spatially in a targeted fashion would likely increase the efficiency of available resources. Indeed, the absence of such a tool is a major concern often expressed by national programme managers; after receiving an alarm signal at the district health office, staff needs clear guidance on where to intervene with early response actions, particularly for highly focal vector control measures such as fogging. A Geographical Information System (GIS) risk mapping tool that includes appropriate evidence-based variables such as vector densities, historical clustering of cases, and/or population movements (yet to be developed and tested) could potentially overcome these difficulties. Research needs include: (1) Developing and pilot testing using GIS software; (2) Field evaluation of the application in high-risk areas; (3) Feasibility, cost, and acceptance studies; and (3) Integration and combined use of the GIS application with EWARS.

Complex intervention strategies targeting larvae and adults as part of community-based campaigns are effective, although it is difficult to disentangle the contribution of each individual component. It is now important to assess how these interventions can be best delivered and evaluate their impact from an operational perspective. Also necessary are studies that can tease apart the individual impacts of interventions that comprise complex community-based campaigns.

According to the available data on successes of house screening in reducing indoor and outdoor vector densities as well as some evidence to suggest an impact on transmission house screening seems to be a promising measure to limit the transmission of Aedes-borne arboviral infections, provided suitable house structure, coverage, acceptability, and sustainability. Additionally, evidence exists in support of complex community-based campaigns to reduce the circulating Aedes population suggesting that these can directly translate into an impact on disease transmission, although further studies are required.

The optimal strategy to deliver vector control tools needs to take into account the principles and key elements of Integrated Vector Management (IVM), which include evidence-based decision making, judicious use of insecticides, and social mobilization and collaboration within the health sector and beyond. Such a strategy requires further research, with the following specific needs: (1) Robust study designs to produce evidence of effectiveness against transmission (2) Health system research focusing on implementation issues (3) Complex intervention strategies targeting larvae and adult mosquitoes as part of community based-campaigns, including delivery of several interventions from an operational perspective.

More specifically, we also need to: (1) Identify the best practices and strategies for a successful partnership model, including social (2) (community) participation. (3)  Analyse the enabling and limiting factors for successful inter-sectoral work at the municipality level.

Conclusions: Additional research will be required for adapting the alert algorithm after implementation of new interventions, such as a dengue vaccine preferably in combination with vector control activities. Research into the above-mentioned areas is essential. The combination of early warning systems, improved vector control, and spatial mapping is expected to increase substantially the efficiency of the limited resources countries can afford. Further research is required to bring these three areas together, some of which is already underway. The use of both community-based and public-sector approaches will empower populations at risk, reduce the per capita cost of interventions, build sustainability, and increase the impact of vector control interventions.

In these days of insecticides and drained swamps, those of us who live in the rich, temperate world have become accustomed to the luxury of not thinking very much about mosquitoes and the risks they carry.

But the insects are still killing more than eight hundred thousand people a year, primarily in Africa.

Winegard’s reminder of their enormous potential for destruction is a timely one for all of us. Globalization is helping to spread a new generation of mosquito-borne illnesses once confined to the tropics, such as dengue, perhaps a thousand years old, and chikungunya and Zika, both of which were first identified in humans only in 1952. Meanwhile, climate change is dramatically expanding the ranges in which mosquitoes and the diseases they carry can thrive. And yet we modern folk are also guilty of believing that our hopes and our technology will somehow make us exempt from the workings of the natural world. The entire time that humanity has been in existence, the mosquito has been proof that we are not.

The writer is  former Head, Department of Medical Sociology,

Institute of Epidemiology, Disease Control & Research (IEDCR)

Dhaka, Bangladesh E-mail: med_sociology_iedcr@yahoo.com

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Published by the Editor on behalf of Independent Publications Limited at Media Printers, 446/H, Tejgaon I/A, Dhaka-1215.
Editorial, News & Commercial Offices : Beximco Media Complex, 149-150 Tejgaon I/A, Dhaka-1208, Bangladesh. GPO Box No. 934, Dhaka-1000.

Editor : M. Shamsur Rahman
Published by the Editor on behalf of Independent Publications Limited at Media Printers, 446/H, Tejgaon I/A, Dhaka-1215.
Editorial, News & Commercial Offices : Beximco Media Complex, 149-150 Tejgaon I/A, Dhaka-1208, Bangladesh. GPO Box No. 934, Dhaka-1000.

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